- (E)-,(Z)-parallel preparative methods for stereodefined β,β-diaryl- and α,β-diaryl-α,β-unsaturated esters: Application to the stereocomplementary concise synthesis of zimelidine
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Parallel and practical methods for the preparation of both (E)- and (Z)-β-aryl1-β-aryl2-α,β-unsaturated esters 1 and (E)- and (Z)-α-aryl1-β-aryl2-α,β-unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N-methylimidazole (NMI)-mediated enol tosylations (14 examples, 70-99 % yield), as well as stereoretentive Suzuki-Miyaura cross-couplings (36 examples, 64-99 % yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)- and (Z)-pure products 1 and 2 by utilizing sequential enol tosylations and cross-coupling reactions. An expeditious and parallel synthesis of (E)- and (Z)-zimelidine (3), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.
- Ashida, Yuichiro,Sato, Yuka,Suzuki, Takeyuki,Ueno, Kanako,Kai, Ken-Ichiro,Nakatsuji, Hidefumi,Tanabe, Yoo
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p. 5934 - 5945
(2015/03/31)
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- Stereoconservative Reductive Methyl- and Dimethylamination of Isomeric 3,3-Diarylpropenals. Synthetic and Mechanistic Studies on Control of the Stereochemistry
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The tertiary allylic amine zimeldine (1Z) and the secondary amine 2Z have been prepared by reductive aminations of (Z)-3-(4-bromophenyl)-3-(3-pyridyl)propenal (3Z) with sodium cyanoborohydride in the presence of dimethylammonium and methylammonium chlorid
- Hoegberg, Thomas,Ulff, Bengt
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p. 4209 - 4214
(2007/10/02)
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- Synthesis of pyridylallylamines related to zimelidine and their inhibition of neuronal monoamine uptake
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Analogues of the antidepressant agent zimelidine [6, (Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine], a selective inhibitor of neuronal 5-hydroxytryptamine reuptake, were synthesized by several routes with the aim of obtaining compounds having a cis configuration (with respect to pyridyl and allylamine). Two methods utilized suitably substituted benzoylpyridines as starting materials. In two other routes, the bromine in 6 was either directly displaced (CN) or converted via the corresponding lithio derivative to H, Cl, I, Me, SiMe3. The configurations were determined by UV, 1H NMR and lanthanide-induced shifts in 1H NMR. The compounds were evaluated as uptake inhibitors by measuring the accumulation of [3H]noradrenaline and 5-hydroxyl[14C]tryptamine in mouse brain slices (in vitro and in vivo). Para substitution favored 5-hydroxytryptamine activity and ortho substitution favored NA activity in the cis series. The in vitro effect on 5-hydroxytryptamine was rather insensitive to variations in the para substituent, whereas pronounced effects in vivo were observed only with Cl, Br (6), and I.
- Hogberg,Ulff,Renyi,Ross
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p. 1499 - 1507
(2007/10/02)
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- Synthesis of 3-Aryl-3-pyridylallylamines Related to Zimelidine via Palladium-Catalyzed Amination
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Reaction of aryl pyridyl ketones 1 with vinylmagnesium bromide followed by acetylation of the products 2 with acetic anhydride/Et3N and with 4-(dimethylamino)pyridine (DMAP) as a catalyst gave acetates 3 in high yields.Treatment of acetates 3 with dimethylamine in the presence of a palladium catalyst produced a mixture of E and Z isomers of 3-aryl-3-pyridylallylamines 4.
- Baeckvall, Jan-E.,Nordberg, Ruth E.,Nystroem, Jan-E.,Hoegberg, Thomas,Ulff, Bengt
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p. 3479 - 3483
(2007/10/02)
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